人视网膜前膜中粘附分子的免疫组织化学观察

目的 观察增生性玻璃体视网膜病变(Proliferative vitreoreti nopathy,PVR)的视网膜前膜(epiretinal membranes,ERM)中粘附分子(ICAM-1,Mac-1) 的表达。方法用免疫组织化学方法对20例复杂视网膜脱离行玻 璃体切割术时剥离的视网膜前膜进行观察。结果ICAM-1和Mac-1分别在18和15例视网膜前膜中表达,两种粘附分子同在12例视网膜前膜中表达。结论ERM中有ICAM-1和Mac-1的表达,提示粘附分子在PVR的发 生发展中有一定作用。（中华眼底病杂志,2000,16：71-138）     

褪黑素对糖尿病大鼠视网膜组织中氧化应激反应及ICAM-1表达的影响

目的观察褪黑素对糖尿病（DM）大鼠氧化应激和视网膜组织中细胞间黏附分子-1（ICAM-1）表达的影响。方法36只Wistar大鼠随机取10只作为正常对照组;其余26只制成DM模型,将造模成功的20只大鼠随机分为褪黑素组和DM组,每组10只。褪黑素组大鼠每日左下腹腔注射10 mg/kg褪黑素进行干预治疗,正常对照组和DM组大鼠不进行治疗。12周后测各组大鼠的体重、血糖、血清一氧化氮（NO）及血清超氧化物歧化酶（SOD）值,并观察大鼠视网膜形态以及ICAM-1表达的不同。结果12周后,与正常对照组比较,DM组和褪黑素组大鼠体重均明显下降（t=5.15,t=3.62;P〈0.05）,血糖均升高（t=69.03,t=45.78;P〈0.05）,而DM组和褪黑素组体重（t=1.88,P=0.09）和血糖（t=-1.41,P=0.19）比较,差异均无统计学意义。与正常对照组比较,DM组和褪黑素组大鼠血清中SOD、NO水平均明显下降（P〈0.05）;与DM组比较,褪黑素组大鼠血清SOD值、血清NO水平均明显升高（t=9.45,t=2.11,P〈0.05）。组织病理学检查显示,DM组和褪黑素组大鼠视网膜结构紊乱,白细胞黏附于血管内皮;免疫组织化学检测显示2组大鼠视网膜标本中ICAM-1颗粒表达于视网膜血管内皮细胞,但褪黑素组较DM组表达明显降低。结论褪黑素可显著提高DM大鼠体内抗氧化能力、降低炎症反应,对DM引起的视网膜损伤有一定的保护作用。     

血清ICAM-1水平与糖尿病性视网膜病变关系的研究

目的:探讨糖尿病患者血清细胞间粘附分子-1(ICAM-1)的水平变化及临床意义。方法:应用ELISA方法测定53例Ⅱ型糖尿病患者及对照组健康人血清中细胞间粘附分子-1的含量。结果:糖尿病视网膜病变患者血清ICAM-1明显高于对照组;糖尿病视网膜病变患者血清ICAM-1明显高于非糖尿病视网膜病变患者;增殖性糖尿病视网膜病变患者高于非增殖性糖尿病视网膜病变患者。结论:ICAM-1可能在DR发病中起着一定的作用。     

血浆内皮素—1与糖尿病视网膜病变发病关系的临床研究

为探索血浆内皮素－１（ＥＴ１）与糖尿病视网病变发生发展的关系，我们用放射免疫法对确诊的糖尿病视网病变患者４４例，糖尿病无视网病变患者１２例以及下沉对照组３０例血浆ＥＴ１水平进行了检测及分析，结果糖尿病患者血浆ＥＴ１浓度显著高于正常对照组，而糖多病变组又明显高于糖再会我视网的变组，其中以增型糖尿 病视网膜病变组血浆ＥＴ１浓度最高。表明糖尿病视网膜病变的发生发展与血浆中ＥＴ１浓度的增加有关。     

人视网膜下膜中ICAM-1及MMP-2的免疫组织化学研究

目的观察增生性玻璃体视网膜病变的视网膜下膜中粘附分子（intercellular adhesion molecules-1，ICAM-1）及基质金属蛋白酶（matrix metculoproteinase-2，MMP-2）的表达。方法用免疫组织化学法对15例复杂视网膜脱离行玻璃体切割术时剥离的视网膜下膜进行观察。结果ICAM-1和MMP-2分别在10例和8例视网膜下膜中表达，二者同时在7例视网膜下膜中表达。结论视网膜下膜中有ICAM-1和MMP-2的表达，提示二者在增生性玻璃体视网膜病变的发生发展中有一定作用。     

HIF-1α及VEGF在增生性糖尿病视网膜病变视网膜前膜中的表达

目的:研究缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)及其靶基因血管内皮生长因子(vascular endothelial growth factor,VEGF)在增殖型性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)视网膜前膜的表达,探讨其在PDR发生发展中的作用。方法:针对26例PDRⅤ～Ⅵ期患者,行玻璃体切除+剥膜术(有合并视网膜脱离者加行视网膜复位术),术中取出视网膜前膜行免疫组织化学染色,观察视网膜前膜中HIT-1α与VEGF和血管内皮标志物CD34的表达。同时行术前血糖、甘油三脂、糖化血红蛋白、是否合并视网脱进行分类并行多因素Logistic回归分析。结果:PDRⅤ～Ⅵ期视网膜前膜血管内皮细胞中,表达HIT-1α者24例(92.3%),VEGF者15例(57.7%),血管内皮标志物CD34者26例(100%)。血管内皮标志物CD34分别与HIT-1α(r=0.556,P=0.028)和VEGF(r=0.745,P=0.001)直线相关。术前血糖、甘油三脂、糖化血红蛋白、是否合并视网脱是PDR视网膜前膜中表达因子HIT-1α,VEGF和CD34表达的相关因素。结论:HIT-1α和VEGF在糖尿病视网膜病变视网膜前膜中明显表达。HIT-1α和VEGF可能在PDR的发病中起重要作用。     

糖尿病视网膜病变患者血浆内皮素-1的变化及意义

糖尿病视网膜病变患者血浆内皮素－１的变化及意义何剑峰鲍连云仇宜解为探讨糖尿病视网膜病变（ｄｉａｂｅｔｉｃｒｅｔｉｎｏｐａｔｈｙ，ＤＲ）发生的相关因素，我们对糖尿病患者血浆内皮素－１（ｅｎｄｏｔｈｅｌｉｎ－１，ＥＴ１）进行了检测分析，现报告如下。１对象...     

ICAM-1和VCAM-1在糖尿病视网膜病变中的作用

糖尿病会造成视网膜很多异常改变,其中包括细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)和血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)的上调,这显示了炎症反应在糖尿病视网膜病变(diabetic retinopathy,DR)发展中发挥了一些作用。本文针对粘附分子ICAM-1和VCAM-1在DR的血管内皮细胞的损伤及其在炎症反应中发挥的重要作用进行了简要分析。     

增生性玻璃体视网膜病变膜免疫组织化学初步研究

通过对增生性玻璃体视网膜病变膜的病理,免疫组化观察,探讨巨噬细胞与ＰＶＲ形成间关系的研究途径。广泛利用免疫组化技术对玻璃体手术中获得的人眼膜进行病理学研究。结果ＰＶＲ的基本病理形态是损伤修复过程。７０％膜标本中检测出巨噬细胞。结论应进一步用免疫组化,分子生物学,免疫电镜,研究巨噬细胞与ＰＶＲ发病间的关系。     

糖尿病视网膜病变粘附分子表达与白细胞粘附的干预性研究进展

糖尿病视网膜病变是糖尿病的重要微血管并发症之一,其发病机制复杂,尚未完全阐明。近年来研究发现白细胞和粘附分子在糖尿病性视网膜病变的病理发生过程中起重要作用。本研究就糖尿病时白细胞和粘附分子表达异常、对视网膜的损害及干预性药物治疗等方面进行了综述。     

糖尿病视网膜病变患者血浆VEGF和CAMS水平的变化及其临床意义

目的探讨糖尿病视网膜病变患者血浆血管内皮细胞生长因子（vascular endothelial growth factor，VEGF）和细胞黏附分子（cellular adhesion molecules，CAMS）水平的变化及其临床意义。方法采用ELISA法检测58例糖尿病视网膜痛变（diabetic retinopathy，DR）患者血浆VEGF、可溶性细胞间黏附分子-1（soluble intercellular adhesion molecule，sICAM—1）和可溶性血管细胞间黏附分子-1（soluble vascular cellular adhesion molecule，sVCAM-1）的变化，并与非糖尿痛视网膜病变（non—diabetic retinopathy，NDR）患者进行比较。结果糖尿病患者血浆VEGF和sICAM—1、sVCAM—1明显高于对照组，差异有显著性（t’=28．581，20．765，t=19．667，P〈0．001）；DR患者血浆VEGF和sICAM—1、sVCAM—1明显高于NDR患者。差异有显著性（t=11．358～16．025，P〈0．001）；PDR患者VEGF和sICAM-1、sVCAM-1明显高于NPDR患者，差异有显著性（t=5．941～14．547，P〈0．001）。NPDR和PDR患者血浆VEGF与siCAM—1、sVCAM—1呈明显的正相关（r=0.617～0．720。P〈0．01）。结论血浆VEGF和sICAM-1、sVCAM—1水平变化参与了DR的发生与发展，且与病变程度有关。     

增生性玻璃体视网膜病变膜剥离标本的免疫组化研究

目的 探讨不同增生性玻璃体视网膜病变(PVR)的增殖特征。方法采用5种特异性抗体对12例PVR膜样本进行免疫组织化学研究。结果成纤维细胞、神经胶质细胞为参与PVR膜的主要细胞成分,视网膜色素上皮细胞(RPE)、巨噬细胞、纤维连接蛋白和新生血管也参与了PVR的病理过程。结论新生血管主要参与了增生性视网膜血管病变的病理过程。增殖膜中增殖的细胞、细胞外基质和血管成分参与了PVR的病理过程并起着不同的作用。     

Expression of integrins in human proliferative diabetic retinopathy membranes

Background: The process of identifying molecules that regulate angiogenesis is critical to the success of candidate therapies for ocular neovascular disease. The purpose of the study was to determine the pattern of expression for integrins and their colocalization with endothelium in membranes from proliferative diabetic retinopathy (PDR).Methods: Clinically categorized membranes were collected from vitreoretinal surgery. A double immunohistochemical staining procedure was used to identify the presence and colocalization of integrins and endothelium. Five integrins were examined.Results: Endothelial markers were robust in all 4 active-stage PDR membranes but absent in the fibrotic-stage PDR membrane. The expression of ανβ3 and β3 integrins on endothelial cells was observed with low to moderate intensity. The expression of α|β| and βa2β| was moderate but was not colocalized with endothelial cells in active-stage PDR membranes. Integrin ανβ5 was not evident in any of the samples used in this study.Interpretation: The results suggest an essential role of integrins ανβ3 and β3 in the pathogenesis of PDR. It is suggested that ανβ3 and β3 are preferred candidate targets for therapeutic development.     

Expression of advanced glycation end products and related molecules in diabetic fibrovascular epiretinal membranes

Purpose: To investigate associations between expressions of advanced glycation end products (AGEs), transforming growth factor‐β (TGF‐β), tumour necrosis factor‐α (TNF‐α) and integrins and correlations between their expression and level of vascularization and proliferative activity in diabetic fibrovascular epiretinal membranes. Methods: Membranes from eight patients with active proliferative diabetic retinopathy and nine patients with inactive proliferative diabetic retinopathy were studied by immunohistochemistry. Results: Blood vessels expressed AGEs, TGF‐β, TNF‐α and α_vβ₃ integrin in 5, 13, 8 and 8 membranes, respectively. Stromal cells expressed AGEs, TNF‐α and α_vβ₃ integrin in 15, 13 and 3 membranes, respectively. There was no immunoreactivity for α_vβ₅, α₅β₁ and α₂β₁ integrins. There were significant correlations between number of blood vessels expressing CD34 and number of blood vessels expressing AGEs (r_s = 0.496; P = 0.043), TGF‐β (r_s = 0.777; P < 0.001) and TNF‐α (r_s = 0.699; P = 0.002). There were significant correlations between number of blood vessels expressing AGEs and number of blood vessels expressing TGF‐β (r_s = 0.532; P = 0.028) and TNF‐α (r_s = 0.626; P = 0.007). The correlation between number of blood vessels expressing TNF‐α and α_vβ₃ integrin was significant (r_s = 0.617; P = 0.008). Number of blood vessels expressing CD34 (P = 0.001), TGF‐β (P = 0.006) and TNF‐α (P = 0.002) and stromal cells expressing AGEs (P = 0.001) and TNF‐α (P = 0.004) were significantly higher in active membranes than in inactive membranes. Conclusion: Interactions of AGEs, TGF‐β, TNF‐α and α_vβ₃ integrin might be involved in pathogenesis of proliferative diabetic retinopathy fibrovascular proliferation.     

视网膜前膜内相关炎性细胞因子的免疫组化研究

目的 研究增生性玻璃体视网膜病变（ｐｒｏｌｉｆｅｒａｔｉｖｅ ｖｉｔｒｅｏｒｅｔｉｎｏｐａｔｈｙ,ＰＶＲ）的视网膜前膜（ｅｐｉｒｅｔｉｎａｌ ｍｅｍｂｒａｎｅｓ,ＥＲＭ）中炎性细胞因子白细胞介素－１β（ｉｎｔｅｒｌｅｕｋｉｎ－１β,ＩＬ－１β）、白细胞介素－６（ｉｎｔｅｒｌｅｕｋｉｎ－６,ＩＬ－６）、白细胞介素－８（ｉｎｔｅｒｌｅｕｋｉｎ－８,ＩＬ－８）和肿瘤坏死因子－α（ｔｕｍｏｒ ｎｅｃｒｏｓｉｓ ｆａｃｔｏｒ－α,ＴＮＦ－α）的表达及其作用。方法 用免疫组织化学方法对１９例复杂性视网膜脱离行玻璃体切割术时剥离的视网膜前膜进行观察。结果 ＩＬ－１β、ＩＬ－６、ＩＬ－８和ＴＮＦ－α分别在９、１２、１１和１５例视网膜前膜中表达,尤其以细胞外基质中明显,４种细胞因子在４例膜中同时表达,仅有１例膜中人表达ＩＬ－６。     

Immunohistochemical study of extracellular matrix components in epiretinal membranes of vitreoproliferative retinopathy and proliferative diabetic retinopathy

PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and other cellular functions are influenced by the surrounding extracellular matrix in normal and wound healing conditions. The formation of epiretinal membranes, a wound healing process, is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In the present study, the authors investigated the expression of various extracellular matrix components and in particular tenascin, fibronectin, laminin, collagen IV, and MMP-3 glycoprotein as well as the expression of glial fibrillary acidic protein in each type of epithelial membrane in order to elucidate the role of these molecules in the formation of these two types of membranes. METHODS: The authors performed immunohistochemistry in 14 PVR and 14 PDR membranes, using antibodies against the above mentioned extracellular matrix components. Tenascin and fibronectin were observed as major components in the extracellular matrix, while laminin and collagen type IV were detected as minor components in both types of membranes. A higher fibronectin expression in PVR compared with PDR membranes was found (p=0.0035). A positive relationship of its expression with the proliferative activity (p=0.15) and collagen type IV expression (p<0.0001) was also observed. RESULTS: Tenascin expression was positively correlated with glial fibrillary acidic protein positive cells in PDR membranes (p=0.04). Collagen type IV localized around vessels was observed with high levels in PDR membranes (p=0.0031). CONCLUSIONS: The results indicated that the extracellular matrix components seem to be involved in PVR and PDR, contributing to tissue remodeling and perhaps by different pathogenetic pathways, which could reflect different stages of development in these two types of membranes.     

实验性视网膜脱离模型中视网膜色素上皮细胞黏附分子的表达

目的观察大鼠视网膜脱离及复位状态下视网膜色素上皮（RPE）细胞黏附分子的表达变化，探讨其与增生性玻璃体视网膜病变（PVR）发生的关系。方法通过视网膜下注射透明质酸钠的方法制造视网膜脱离的动物模型。在不同的时间点摘除眼球，制作冰冻切片，进行免疫组织化学及免疫荧光染色，比较RPE细胞上几种黏附分子，包括神经钙粘素、上皮钙粘素、整合素α5、整合素β1，以及纤维连接蛋白（FN）在正常视网膜、脱离的视网膜、复位的视网膜中的表达情况。结果几种黏附分子在脱离区的RPE细胞上的表达均明显高于正常视网膜以及脱离后复位的视网膜。结论视网膜脱离会导致RPE细胞上几种重要的黏附分子的表达增加，视网膜复位可逆转此种变化。视网膜脱离可能是PVR发生的始动因素。